Whole body leucine flux was measured in eight patients with nephrotic syndrome and in five normal subjects by primed-constant intravenous infusion of L-[l-13C]leucine. Plasma enrichment of 13C leucine and 13CKIC were measured by gas chromatography/mass spectrometry and exhaled 13CO2 by isotope ratio mass spectrometry. All parameters of leucine flux, including the rates of leucine oxidation, leucine release from protein degradation and, to a lesser extent, leucine incorporation into protein, were reduced in the nephrotic patients. The values (means (SD, umol/kg/hr) of the different parameters in the nephrotic patients and the controls were: Leucine derived from protein degradation, 99(6 and 117; leucine oxidation rate 15(7 and 22(3, (p=0.04) the rate of leucine incorporation into whole body protein, 8484+10 and 95+6, (p=0.04), and net leucine balance which is the difference between the rates of protein synthesis and degradation was -15+7 and -22+3, (p=0.04). T he negative values are due to the fact that measurements were made after a 12 hr fast. Protein turnover rate, calculated from leucine flux, were 3.9+0.4 and 4.7+0.3 g/kg/day in the nephrotic and the control groups (p=0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/day. For days prior to study the patients ingested a controlled diet consisting of 0.84 g protein/kg/d and 33.3(9 Kcal/kg/day. Thus, at this level of protein/energy intake, nephrotic patients maintained nitrogen balance perhaps because of a metabolic adaptation that resulted in a down regulation of protein degradation and amino acid oxidation rates.